ABSTRACT

Myocardial remodeling occurs in response to a prolonged cardiovascular stress and is characterized by a cascade of compensatory structural events within the myocardium. This remodeling process has been observed following myocardial infarction (MI), with hypertrophy, or cardiomyopathic disease. Progressive left ventricular (LV) dilation in patients with congestive heart failure (CHF) is associated with a greater incidence of morbidity and mortality. Furthermore, pharmacological interventions that provide a beneficial effect on survival in CHF patients attenuate the rate and extent of LV dilation. These observational data suggest that interventions that directly alter the LV myocardial remodeling process hold therapeutic promise in the setting of CHF. A number of cellular and extracellular factors probably contribute to the complex process of myocardial remodeling. For example, myocardial remodeling following MI includes changes in coronary vascular structure and function, myocyte loss, hypertrophy of remaining myocytes, and increased size and number of non-myocyte cells. Collectively, these alterations result in non-uniform changes in LV myocardial wall geometry. While myocardial remodeling is accompanied by modifications in the cellular constituents of the LV myocardium, most notably those of the remaining viable myocytes, significant alterations in the structure and composition of the extracellular matrix (ECM) occur. The goals of this chapter are to revisit and revise the concepts regarding structure and function of the myocardial ECM and then to place these concepts in reference to hypertrophy and the progression to failure.